The objective of this project is to study the expression of Hemopoietic-histocompatibility (Hh) gene products on the surface of normal hemopoietic stem cells and of neoplastic cells originating from hemopoietic and other tissues; and furthermore to establish the conditions under which recognition of these antigenic gene products by the host's immune system leads to suppression of target cells. Hh genes, not inherited codominantly, are the determinants of tissue-specific cell components responsible for the acute rejection of parental, allogeneic and xenogeneic bone marrow grafts by heavily irradiated mice. The rejection of these grafts involves unusual mechanisms as it is effected by cell types which are relatively radioresistant, independent of the thymus for differentiation and maturation, sensitive to antilymphocyte and antimacrophage agents, capable of immunologic recognition and of causing graft destruction within 18-96 hours from transplantation. The anti-Hh reactivity detected through grafting of hemopoietic cells may normally regulate hemopoiesis and suppress leukemogenesis. Experiments will be performed in vivo (bioassays for resistance to graft proliferation) and in vitro (induction of specific cytotoxicity, assessment of "natural" cytotoxicity), and designed so as to detect and quantitate: (1) Changes of Hh-gene expression occurring early during virus induced leukemic transformation of hemopoietic cells and in established tumor cell lines. (2) Selective expression of Hh genes in defined tumors generating tumor-specific cell surface properties (compared with normal cells of adult mice). (3) Host reactions to Hh antigens in allogeneic, semisyngeneic (parent-to-F1 hybrid), syngeneic, and autochthonous tumor-host relationships. (4) Cell types responsible for recognition and effector function in reactions to Hh-incompatible and virus-transformed cells.